Fried Shalev, Avigdor Abraham, Bielorai Bella, Meir Amilia, Besser Michal J, Schachter Jacob, Shimoni Avichai, Nagler Arnon, Toren Amos, Jacoby Elad
Division of Pediatric Hematology and Oncology, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Bone Marrow Transplant. 2019 Oct;54(10):1643-1650. doi: 10.1038/s41409-019-0487-3. Epub 2019 Feb 26.
Autologous T cells transduced with CD19-directed chimeric antigen receptors have recently been approved by several regulatory agencies for the treatment of relapsed and refractory leukemia and lymphoma, after demonstrating remarkable remission rate in advanced patients. The most common adverse events reported are cytokine-release syndrome (CRS), neurotoxicity, and hematologic toxicity. Here, we focus on early and late cytopenia occurring after CD19 CAR-T cells in 38 patients treated with CD19 CAR-T cells. Neutropenia, thrombocytopenia, and anemia occur frequently (94, 80, and 51%, respectively) after CAR-T cell infusion, and are associated with a biphasic nature, as in 93% of patients hematologic toxicity occurs after 21 days from cell infusion. Late hematologic toxicity was more common in patients with high grade CRS and in patients treated after a recent stem cell transplantation. Interestingly, since these events occur late after the lymphodepleting chemotherapy and after resolution of CRS, we found perturbations in SDF-1 levels to correlate with events of late neutropenia, likely associated with B-cell recovery.
用CD19导向的嵌合抗原受体转导的自体T细胞最近已被多个监管机构批准用于治疗复发难治性白血病和淋巴瘤，此前在晚期患者中显示出显著的缓解率。报告的最常见不良事件是细胞因子释放综合征（CRS）、神经毒性和血液学毒性。在此，我们关注38例接受CD19 CAR-T细胞治疗的患者在接受CD19 CAR-T细胞治疗后出现的早期和晚期血细胞减少。中性粒细胞减少、血小板减少和贫血在CAR-T细胞输注后频繁发生（分别为94%、80%和51%），并且具有双相性，因为93%的患者血液学毒性在细胞输注后21天出现。晚期血液学毒性在高级别CRS患者和近期干细胞移植后接受治疗的患者中更为常见。有趣的是，由于这些事件发生在淋巴细胞清除化疗后较晚时间且在CRS缓解后，我们发现SDF-1水平的扰动与晚期中性粒细胞减少事件相关，可能与B细胞恢复有关。
